(1) Field of the Invention
The present invention relates to an agent for prevention and remedy of injuries caused by ischemia.
(2) Description of the Related Art
The ischemic disease, a kind of the injury caused by ischemia, is a morbid state caused by bleeding or abnormality of blood properties. As the ischemic disease, there can be mentioned cardiac infarction, cerebral thromobosis, angina pectoris and disseminated intravascular coagulation (DIC) caused by exogenous or endogenous hyperfunction of the coagulating mechanism, which is due to the activation of thromboplastin released from the texture injured by cancer, systemic infection with bacteria or fungi, or hypoxemia. An antithrombotic agent or heparin has been used for the remedy of the ischemic disease, but the effect is yet insufficient. Furthermore, any other agent has not been clinically effectively used for this purpose.
As another injury caused by ischemia, there can be mentioned an injury of an organ for transplantation. Namely, success of transplantation depends greatly on the preservation of the tissue activity at the harvest of the organ, during the storage of the harvested organ and at the transplantation (hereinafter referred to as "preservation").
As the method for the preservation of an harvested organ, which is widely used in the clinical field, there can be mentioned a simple hypothermic immersion preservation and hypothermic perfusion preservation. As the preservation solution generally used, there can be mentioned an electrolyte solution called "intracellular solution" for the simple hypothermic immersion preservation. For example, Collins solution and modified Collins solution are used. For the hypothermic perfusion preservation, a solution prepared by adding electrolytes to plasma components, which is called "extracellular solution", is used. As the means for improving the long-period preservability, there can be mentioned a method in which dimethyl sulfoxide, glycerol or the like is added, as disclosed in Japanese Patent Publication No. 56201/1986, a method in which a protein or glycoprotein modified with a higher alcohol, a fatty acid or an amino acid ester is added, as disclosed in Japanese Patent Application Laid-Open Specification No. 27901/1986, and a method in which a plasminogen activator is incorporated, as disclosed in Japanese Patent Application Laid-Open Specification No. 226928/1987.
As the important cause of the injury to an organ, there can be mentioned generation of active oxygen by ischemia at the harvest of the organ, the preservation of the harvested organ and the transplantation operation, or at the perfusion of an oxygenated preservation solution and reperfusion of blood after the transplantation. Accordingly, there has been tried an organpreserving method in which a superoxide dismutase or catalase is used as oxygen radical scavengers' [see, for example, J. R. Stewart et al., Ann. Thorac. Surg., 42, 390 (1986)].
A freeze preservation method can be considered as the organ preserving method, but this method is not effective because an appropriate agent which prevents freeze injury has not been developed.
In these organ preserving methods, it is only in case of the preservation of the kidney that the improvement of the preservability is attained and there is no appropriate method for the preservation of other organs. Especially in case of preserving, the heart and lung therefore, it is said that the upper limit of the preservation time is 6 hours.